Anesthetizing composition and method

ABSTRACT

ALIPHATIC ETHER COMPOUNDS OF THE FORMULA   CF3-(CH(-F))N-C(-O-CH3)2-X   WHEREIN N IS ZERO OR ONE, AND -X IS -CF3 OR -H WHEN N IS ZERO AND IS -OCH3 WHEN N IS ONE, ARE USEFUL AS INHALATION ANESTHETICS.

United States Patent '0 ABSTRACT OF THE DISCLOSURE Aliphatic ethercompounds of the formula CH: 0 m en F\ iJ-x b011, wherein n is zero orone, and X is CF or -H when n is zero and is OCH when n is one, areuseful as inhalation anesthetics.

This invention relates to certain aliphatic ether compounds and theiruse in producing anesthesia in anesthetic-susceptible mammals.

The compounds of the present invention have the formula wherein n iszero or one, and X is -CF or -H when n is zero and is OCH when n is one.These compounds lend themselves to eifective use as inhalant anestheticsin respirable mixtures containing life-supporting concentrations ofoxygen, with or without other inhalation anesthetics, such as nitrousoxide. Administration of the compounds may be by any of the well knowntechniques for administering general inhalation anesthetics, for exampleby using the open drip, semi-closed or closed systems.

The effective amounts of the compounds of this invention to be employeddepend on the level of anesthesia to which the mammal is to be brought,the rate at which anesthesia is to be induced, and the length of timeover which anesthia is to be maintained. Minor volume percentages of thecompound in oxygen can often be employed. The amount used should besuflicient to provide a significant anesthetic effect, but not so muchas to produce unacceptable deleterious side efiects. Vaporconcentrations at which the compounds of this invention may often beused are about 0.5 to 6 volume percent, with the concentration actuallyemployed depending on the choice of anesthetic; for instance,1,1,l,2-tetrafluoro- 3,3,3-trimethoxypropane may often be used in anamount of about 0.5 to 2.8%, trifluoroacetaldehyde dimethyl acetal mayoften be used in an amount of about 2 to 6%, and dimethylketal ofhexafluoroacetone may often be used in an amount of about 3 to 6%. Theamount of anesthesia to be used can be regulated, starting with a smallamount of the ether and gradually increasing the amount until thedesired plane of anesthesia is reached. By then monitoring the physicalreactions of the mammal, as is the usual procedure, the duration andplane of anesthesia can be readily controlled.

The compounds of this invention are also easily miscible with otherorganic liquids, including fats and oils,

and have useful solvent properties, for example as s0lvents forfluorinated olefins and other fluorinated materials, such as fluorowaxes. The compounds of this invention may be used to prepare pastes anddispersions o fsuch materials useful for coatings and the like, and maybe used as degreasing agents. In the latter capacity, for example, theether compounds of this invention can be used as solvents to removegrease or other oily substances from metal surfaces that are to bepainted.

The following examples illustrate the preparation of the compounds ofthe present invention.

EXAMPLE I This example illustrates the preparation of 1,l,1,2-tetra-fluoro-3,3,3-trimethoxypropane.

Perfluoropropene (48.7 g.) was added slowly to a cold (05 C.) solutionof NaOCH (35.2 g.) in methanol (140 ml.) over a period of 1 hour,followed by warming at 55 C. for 5 hours. The mixture was poured intowater and neutralized, and the crude product was isolated by refluxingthe aqueous mixture into a Dean- Stark tube. Fractional distillation ofthe dried (over K CO product gave a fraction boiling at 100 C. fromwhich CF CHFC(OCH was obtained by preparative chromatography.

This normally liquid ether has a boiling point of 118 C., a specificgravity of 1.27, a vapor pressure at 25 C. of 21 mm. Hg, a refractiveindex (n of 1.3497, and a mild odor. The compound is nonflammable.

EXAMPLE II This example illustrates the preparation of the dimethylketalof hexaflouroacetone.

Hexafluoroacetone (43 g.) was added to methanol (7.5 g.) at -40 C.followed by warming the mixture to room temperature. Diethyl ether (60ml.) and dimethylsulfate (35.7 g.) were added, followed by gradualaddition of anhydrous, granular K 00 (43 g.). The mixture was stirredfor 7.5 hours. The mixture was diluted with water followed by extractingwith diethyl ether. Ether was stripped from the dried (K CO extractleaving a crude product from which 27 g. of pure was obtained bypreparative chromatography.

Calculated for C H F O F, 53.8%. Found: F, 53.9%. This normally liquidcompound has a boiling point of 85 C., a specific gravity of 1.34, avapor pressure at 25 C. of 80 mm. Hg, a refractive index (n of 1.3054,and

a faint, sweet odor. It is nonflammable.

EXAMPLE III This example illustrates the preparation oftrifluoroacetaldehyde dimethyl acetal. Anhydrous, granular K 00 (43 g.)was added gradually to a solution of commercially obtainedtrifluoroacetaldehyde methyl hemiacetal (34 g.) and dimethylsulfate (36g.) in diethyl ether at 20-25 C. followed by stirring for 10 hours. Themixture was poured into water, then extracted with diethyl ether.Diethyl ether was stripped from the dried (over K CO extracts, and pureCF CH(OCH (15 g.) was separated from the crude product by preparativechromatography.

Calculated for C H F O F, 39.6%. Found: F, 39.3%.

This normally liquid compound has a boiling point of 78.5 C., a specificgravity of 1.28, a vapor pressure at 25 C. of mm. Hg, and 'a refractiveindex (n of 1.3222. The compound is flammable.

In order to determine the potency of the aliphatic ethers of the presentinvention as inhalation anesthetics in combination with oxygen, testswere carried out on mice. The compounds tested were at least 99.5% pureas determined by vapor phase chromatography. In the tests, the ethercompound is administered to test mice by a standard procedure in which ameasured quanttiy of the agent is placed in a laboratory jar and allowedto completely vaporize so as to give a calculated vapor concentration.The test mice are then quickly placed in the jar and observed.Anesthesia is determined by observing the righting reflex of the mice.Recovery time is measured beginning when the mice are transferred fromthe test jar to room air and ending when the mice are observed to beable to walk.

In such tests the 1,1,1,2-tetrafluoro-3,3,3-trimethoxypropane inducedanesthesia in the mice in 1 minute when used at a vapor concentration of1%. Induction was smooth, but there were bursts of rapid limb tremorssometimes one limb only-throughout maintenance of the anesthesia. Thesetremors, which at times had the appearance of a focal convulsion,continued with much squeaking for 3 minutes into the recovery period,which lasted 4 minutes 35 seconds. Some analgesia was evident duringanesthesia. When used at 2% vapor concentration, essent-ially the sameresults were observed, except that the induction period was shortened to25 seconds and the recovery period was lengthened to 7 minutes 31seconds.

Use of 4% vapor concentration of the dimethylketal of hexafluoroacetoneresulted in induction of anesthesia in 1 minute 10 seconds. Theinduction was accompanied by much excitement. The anesthesia was lightand the mice responded to stimulation while under it. When 5% vaporconcentration was used, a deeper anesthesia was induced in 49 seconds;recovery required 1 minute 34 seconds.

The trifluoroacetaldehyde dimethyl acetal, when used at 2.5% vaporconcentration, induced a light anesthesia in 2 minutes 13 seconds. Anuneventful recovery therefrom occurred in 30 seconds. At 4.0% vaporconcentration, the induction time was shortened to 1 minute 11 secondsand the recovery time was lengthened to 2 minutes 8 seconds. Someanalgesia was evident along with the anesthesia.

While there has been described what are at present considered to be thepreferred embodiments of the invention, it will be understood thatvarious modifications may be made therein which are within the truespirit and scope of the invention.

We claim:

1. An inhalant anesthetic composition comprising an aliphatic ethercompound of the formula CFaCHF-CH and oxygen in suitable proportions foruse as an anesthetic.

2. A method of anesthetizing an anesthetic-susceptible mammal whichcomprises administering to the mammal an anesthetically-effective amountof an aliphatic ether compound of the formula OFi-OHF- H as aninhalation anesthetic, while administering life-supporting amounts ofoxygen.

References Cited Chemical Abstracts, vol. 60, Formula Index, January-June 1964, page 47F.

JEROME D. GOLDBERG, Primary Examiner UNITED STATES PATENT OFFICECERTIFICATE OF CORRECTION PATENT NO. 3,745,220

DATED July 10, 1973 INVENTOR(S) ROSS c. TERRELL and GEORGE L. MOORE Itis certified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

In claim '1 the formula should read:

OCH

In claim 2 the formula should read:

(IJCH3 CF3 ?-H OCH3 Signed and Scaled this [SEAL] thirtieth Day OfSeptember 1975 Arrest."

RUTH C. MASON I 4 mnusxwner of Parents and Trademarks

